The cellular location and carbohydrate specificies of a glycoprotein recognition system on rat hepatic sinusoidal cells have been determined. Purified preparations of enothelial, Kupffer and parenchymal cells have been prepared in situ by collagenase liver perfusion, centrifugation on Percoll gradients and centrifugal elutriation. 125I-labeled agalactoorosomucoid (AGOR), an N-acetylglucosamine-terminated glycoprotein, is selectively and specifically taken up in vitro by endothelial cells. Glucose and a glucose-albumin conjugate competitively inhibited this uptake process over a wide range of concentrations. Uptake by cells from fasted rats was enhanced, but uptake by cells from fasted or fed diabetic rats was normal. The in vivo hepatic uptake and catabolism of 125I-AGOR were slower in diabetic than normal rats. These findings indicate that 1) the hepatic receptors which recognize N-acetylglucosamine/mannose terminated glycoproteins are located on endothelial cells, 2) these receptors are glucose sensitive, 3) fasting increases the number of these receptors and 4) diabetes mellitus abolishes this effect of fasting and impairs the function of this receptor in vivo. The results of this study suggest a mechanism for abnormal glycoprotein metabolism in diabetes mellitus.